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Volume 171, Issue 2

100+ years of phase variation: the premier bacterial bet-hedging phenomenon Open Access

Abstract

Stochastic, reversible switches in the expression of flagella variants were first described by Andrewes in 1922. Termed phase variation (PV), subsequent research found that this phenomenon was widespread among bacterial species and controlled expression of major determinants of bacterial–host interactions. Underlying mechanisms were not discovered until the 1970s/1980s but were found to encompass intrinsic aspects of DNA processes (i.e. DNA slippage and recombination) and DNA modifications (i.e. DNA methylation). Despite this long history, discoveries are ongoing with expansions of the phase-variable repertoire into new organisms and novel insights into the functions of known loci and switching mechanisms. Some of these discoveries are somewhat controversial as the term ‘PV’ is being applied without addressing key aspects of the phenomenon such as whether mutations or epigenetic changes are reversible and generated prior to selection. Another ‘missing’ aspect of PV research is the impact of these adaptive switches in real-world situations. This review provides a perspective on the historical timeline of the discovery of PV, the current state-of-the-art, controversial aspects of classifying phase-variable loci and possible ‘missing’ real-world effects of this phenomenon.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): bistability , contingency loci , instability , localised hypermutation , phase variation , phasevarion and phasome
Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (Award BB/M01116X/1)
    • Principal Award Recipient: JackClark
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2026-01-13

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100+ years of phase variation: the premier bacterial bet-hedging phenomenon
Microbiology 171, 001537 (2025); https://doi.org/10.1099/mic.0.001537
/content/journal/micro/10.1099/mic.0.001537
/content/journal/micro/10.1099/mic.0.001537
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